Cited by 269Microtubule and mitosis dynamicsCellular transport and secretionAutophagy in Disease and Therapy

BORC functions upstream of kinesins 1 and 3 to coordinate regional movement of lysosomes along different microtubule tracks

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Guardia, Carlos M., Farías, Ginny G., Jia, Rui, Pu, Jing, Bonifacino, Juan S.·2016·Cell Reports

Abstract

The multiple functions of lysosomes are critically dependent on their ability to undergo bidirectional movement along microtubules between the center and the periphery of the cell. Centrifugal and centripetal movement of lysosomes is mediated by kinesin and dynein motors, respectively. We recently described a multi-subunit complex named BORC that recruits the small GTPase Arl8 to lysosomes to promote their kinesin-dependent movement toward the cell periphery. Here, we show that BORC and Arl8 function upstream of two structurally distinct kinesin types: kinesin-1 (KIF5B) and kinesin-3 (KIF1Bβ and KIF1A). Remarkably, KIF5B preferentially moves lysosomes on perinuclear tracks enriched in acetylated α-tubulin, whereas KIF1Bβ and KIF1A drive lysosome movement on more rectilinear, peripheral tracks enriched in tyrosinated α-tubulin. These findings establish BORC as a master regulator of lysosome positioning through coupling to different kinesins and microtubule tracks. Common regulation by BORC enables coordinate control of lysosome movement in different regions of the cell.

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  1. Bagshaw RD Callahan JW Mahuran DJ The Arf-family protein, Arl8b, is involved in the spatial distribution of lysosomes. Biochem Biophys Res Commun 2006 344 1186 1191 16650381
  2. Ballabio A The awesome lysosome. EMBO Mol Med 2016 8 73 76 26787653 PMC4734841
  3. Bentley M Decker H Luisi J Banker G A novel assay reveals preferential binding between Rabs, kinesins, and specific endosomal subpopulations. J Cell Biol 2015 208 273 281 25624392 PMC4315250
  4. Bielska E Schuster M Roger Y Berepiki A Soanes DM Talbot NJ Steinberg G Hook is an adapter that coordinates kinesin-3 and dynein cargo attachment on early endosomes. J Cell Biol 2014 204 989 1007 24637326 PMC3998801
  5. Boucrot E Henry T Borg JP Gorvel JP Meresse S The intracellular fate of Salmonella depends on the recruitment of kinesin. Science 2005 308 1174 1178 15905402
  6. Brown CL Maier KC Stauber T Ginkel LM Wordeman L Vernos I Schroer TA Kinesin-2 is a motor for late endosomes and lysosomes. Traffic 2005 6 1114 1124 16262723
  7. Burgoyne RD Norman KM Alpha-tubulin is not detyrosylated during axonal transport. Brain Res 1986 381 113 120 2428430
  8. Cai D McEwen DP Martens JR Meyhofer E Verhey KJ Single molecule imaging reveals differences in microtubule track selection between Kinesin motors. PLoS Biol 2009 7 e1000216 19823565 PMC2749942
  9. Cai Q Lu L Tian JH Zhu YB Qiao H Sheng ZH Snapin-regulated late endosomal transport is critical for efficient autophagy-lysosomal function in neurons. Neuron 2010 68 73 86 20920792 PMC2953270
  10. Cambray-Deakin MA Burgoyne RD Posttranslational modifications of alpha-tubulin: acetylated and detyrosinated forms in axons of rat cerebellum. J Cell Biol 1987 104 1569 1574 3294857 PMC2114518
  11. Chen S Han M Chen W He Y Huang B Zhao P Huang Q Gao L Qu X Li X KIF1B promotes glioma migration and invasion via cell surface localization of MT1-MMP. Oncol Rep 2016 35 971 977 26576027
  12. Cheng XT Zhou B Lin MY Cai Q Sheng ZH Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes. J Cell Biol 2015 209 377 386 25940348 PMC4427784
  13. DeBoer SR You Y Szodorai A Kaminska A Pigino G Nwabuisi E Wang B Estrada-Hernandez T Kins S Brady ST Conventional kinesin holoenzymes are composed of heavy and light chain homodimers. Biochemistry 2008 47 4535 4543 18361505 PMC2644488
  14. Delevoye C Miserey-Lenkei S Montagnac G Gilles-Marsens F Paul-Gilloteaux P Giordano F Waharte F Marks MS Goud B Raposo G Recycling endosome tubule morphogenesis from sorting endosomes requires the kinesin motor KIF13A. Cell Rep 2014 6 445 454 24462287 PMC3928541
  15. Dong Z Xu X Du L Yang Y Cheng H Zhang X Li Z Wang L Li J Liu H Leptin-mediated regulation of MT1-MMP localization is KIF1B dependent and enhances gastric cancer cell invasion. Carcinogenesis 2013 34 974 983 23354307
  16. Dumont A Boucrot E Drevensek S Daire V Gorvel JP Pous C Holden DW Meresse S SKIP, the host target of the Salmonella virulence factor SifA, promotes kinesin-1-dependent vacuolar membrane exchanges. Traffic 2010 11 899 911 20406420
  17. Friedman DS Vale RD Single-molecule analysis of kinesin motility reveals regulation by the cargo-binding tail domain. Nat Cell Biol 1999 1 293 297 10559942
  18. Garg S Sharma M Ung C Tuli A Barral DC Hava DL Veerapen N Besra GS Hacohen N Brenner MB Lysosomal trafficking, antigen presentation, and microbial killing are controlled by the Arf-like GTPase Arl8b. Immunity 2011 35 182 193 21802320 PMC3584282
  19. Harada A Takei Y Kanai Y Tanaka Y Nonaka S Hirokawa N Golgi vesiculation and lysosome dispersion in cells lacking cytoplasmic dynein. J Cell Biol 1998 141 51 59 9531547 PMC2132725
  20. Hoepfner S Severin F Cabezas A Habermann B Runge A Gillooly D Stenmark H Zerial M Modulation of receptor recycling and degradation by the endosomal kinesin KIF16B. Cell 2005 121 437 450 15882625
  21. Hofmann I Munro S An N-terminally acetylated Arf-like GTPase is localised to lysosomes and affects their motility. J Cell Sci 2006 119 1494 1503 16537643
  22. Hollenbeck PJ Swanson JA Radial extension of macrophage tubular lysosomes supported by kinesin. Nature 1990 346 864 866 1697403
  23. Huang CF Banker G The translocation selectivity of the kinesins that mediate neuronal organelle transport. Traffic 2012 13 549 564 22212743 PMC3967410
  24. Huo L Yue Y Ren J Yu J Liu J Yu Y Ye F Xu T Zhang M Feng W The CC1-FHA tandem as a central hub for controlling the dimerization and activation of kinesin-3 KIF1A. Structure 2012 20 1550 1561 22863567
  25. Jacobson C Schnapp B Banker GA A change in the selective translocation of the Kinesin-1 motor domain marks the initial specification of the axon. Neuron 2006 49 797 804 16543128
  26. Jordens I Fernandez-Borja M Marsman M Dusseljee S Janssen L Calafat J Janssen H Wubbolts R Neefjes J The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors. Curr Biol 2001 11 1680 1685 11696325
  27. Kanai Y Okada Y Tanaka Y Harada A Terada S Hirokawa N KIF5C, a novel neuronal kinesin enriched in motor neurons. J Neurosci 2000 20 6374 6384 10964943 PMC6772948
  28. Klopfenstein DR Vale RD The lipid binding pleckstrin homology domain in UNC-104 kinesin is necessary for synaptic vesicle transport in Caenorhabditis elegans. Mol Biol Cell 2004 15 3729 3739 15155810 PMC491832
  29. Korolchuk VI Saiki S Lichtenberg M Siddiqi FH Roberts EA Imarisio S Jahreiss L Sarkar S Futter M Menzies FM Lysosomal positioning coordinates cellular nutrient responses. Nat Cell Biol 2011 13 453 460 21394080 PMC3071334
  30. Kreis TE Microtubules containing detyrosinated tubulin are less dynamic. EMBO J 1987 6 2597 2606 3315650 PMC553680
  31. Lipka J Kapitein LC Jaworski J Hoogenraad CC Microtubule-binding protein doublecortin-like kinase 1 (DCLK1) guides kinesin-3-mediated cargo transport to dendrites. EMBO J 2016 35 302 318 26758546 PMC4741305
  32. Matsushita M Tanaka S Nakamura N Inoue H Kanazawa H A novel kinesin-like protein, KIF1Bbeta3 is involved in the movement of lysosomes to the cell periphery in non-neuronal cells. Traffic 2004 5 140 151 15086790
  33. Matteoni R Kreis TE Translocation and clustering of endosomes and lysosomes depends on microtubules. J Cell Biol 1987 105 1253 1265 3308906 PMC2114818
  34. Moughamian AJ Osborn GE Lazarus JE Maday S Holzbaur EL Ordered recruitment of dynactin to the microtubule plus-end is required for efficient initiation of retrograde axonal transport. J Neurosci 2013 33 13190 13203 23926272 PMC3735891
  35. Mrakovic A Kay JG Furuya W Brumell JH Botelho RJ Rab7 and Arl8 GTPases are necessary for lysosome tubulation in macrophages. Traffic 2012 13 1667 1679 22909026
  36. Nakata T Hirokawa N Point mutation of adenosine triphosphate-binding motif generated rigor kinesin that selectively blocks anterograde lysosome membrane transport. J Cell Biol 1995 131 1039 1053 7490281 PMC2200001
  37. Nakata T Hirokawa N Microtubules provide directional cues for polarized axonal transport through interaction with kinesin motor head. J Cell Biol 2003 162 1045 1055 12975348 PMC2172855
  38. Neef R Klein UR Kopajtich R Barr FA Cooperation between mitotic kinesins controls the late stages of cytokinesis. Curr Biol 2006 16 301 307 16461284
  39. Okada Y Yamazaki H Sekine-Aizawa Y Hirokawa N The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors. Cell 1995 81 769 780 7539720
  40. Pack-Chung E Kurshan PT Dickman DK Schwarz TL A Drosophila kinesin required for synaptic bouton formation and synaptic vesicle transport. Nat Neurosci 2007 10 980 989 17643120
  41. Pan X Ou G Civelekoglu-Scholey G Blacque OE Endres NF Tao L Mogilner A Leroux MR Vale RD Scholey JM Mechanism of transport of IFT particles in C. elegans cilia by the concerted action of kinesin-II and OSM-3 motors. J Cell Biol 2006 174 1035 1045 17000880 PMC2064394
  42. Pernigo S Lamprecht A Steiner RA Dodding MP Structural basis for kinesin-1:cargo recognition. Science 2013 340 356 359 23519214 PMC3693442
  43. Pu J Schindler C Jia R Jarnik M Backlund P Bonifacino JS BORC, a multiprotein complex that regulates lysosome positioning. Dev. Cell 2015 33 176 188 25898167 PMC4788105
  44. Quintyne NJ Gill SR Eckley DM Crego CL Compton DA Schroer TA Dynactin is required for microtubule anchoring at centrosomes. J Cell Biol 1999 147 321 334 10525538 PMC2174233
  45. Rahman A Kamal A Roberts EA Goldstein LS Defective kinesin heavy chain behavior in mouse kinesin light chain mutants. J Cell Biol 1999 146 1277 1288 10491391 PMC2156125
  46. Reddy A Caler EV Andrews NW Plasma membrane repair is mediated by Ca(2+)-regulated exocytosis of lysosomes. Cell 2001 106 157 169 11511344
  47. Rosa-Ferreira C Munro S Arl8 and SKIP act together to link lysosomes to kinesin-1. Dev Cell 2011 21 1171 1178 22172677 PMC3240744
  48. Santama N Krijnse-Locker J Griffiths G Noda Y Hirokawa N Dotti CG KIF2beta, a new kinesin superfamily protein in non-neuronal cells, is associated with lysosomes and may be implicated in their centrifugal translocation. EMBO J 1998 17 5855 5867 9774330 PMC1170913
  49. Sasaki A Nakae I Nagasawa M Hashimoto K Abe F Saito K Fukuyama M Gengyo-Ando K Mitani S Katada T Arl8/ARL-8 functions in apoptotic cell removal by mediating phagolysosome formation in Caenorhabditis elegans. Mol Biol Cell 2013 24 1584 1592 23485564 PMC3655818
  50. Schiefermeier N Scheffler JM de Araujo ME Stasyk T Yordanov T Ebner HL Offterdinger M Munck S Hess MW Wickstrom SA The late endosomal p14-MP1 (LAMTOR2/3) complex regulates focal adhesion dynamics during cell migration. J Cell Biol 2014 205 525 540 24841562 PMC4033770
  51. Schuchardt I Assmann D Thines E Schuberth C Steinberg G Myosin-V, Kinesin-1, and Kinesin-3 cooperate in hyphal growth of the fungus Ustilago maydis. Mol Biol Cell 2005 16 5191 5201 16120650 PMC1266418
  52. Song Y Brady ST Post-translational modifications of tubulin: pathways to functional diversity of microtubules. Trends Cell Biol 2015 25 125 136 25468068 PMC4344850
  53. Steffan JJ Williams BC Welbourne T Cardelli JA HGF-induced invasion by prostate tumor cells requires anterograde lysosome trafficking and activity of Na+-H+ exchangers. J Cell Sci 2010 123 1151 1159 20215403 PMC2844323
  54. Tuli A Thiery J James AM Michelet X Sharma M Garg S Sanborn KB Orange JS Lieberman J Brenner MB Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell-mediated cytotoxicity. Mol Biol Cell 2013 24 3721 3735 24088571 PMC3842998
  55. van Bergeijk P Hoogenraad CC Kapitein LC Right Time, Right Place: Probing the Functions of Organelle Positioning. Trends Cell Biol 2016 26 121 134 26541125
  56. Wu YE Huo L Maeder CI Feng W Shen K The balance between capture and dissociation of presynaptic proteins controls the spatial distribution of synapses. Neuron 2013 78 994 1011 23727120 PMC3898717
  57. Zhao C Takita J Tanaka Y Setou M Nakagawa T Takeda S Yang HW Terada S Nakata T Takei Y Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell 2001 105 587 597 11389829
  58. Zheng Q Ahlawat S Schaefer A Mahoney T Koushika SP Nonet ML The vesicle protein SAM-4 regulates the processivity of synaptic vesicle transport. PLoS Genet 2014 10 e1004644 25329901 PMC4199485
  59. Zhou B Cai Q Xie Y Sheng ZH Snapin recruits dynein to BDNF-TrkB signaling endosomes for retrograde axonal transport and is essential for dendrite growth of cortical neurons. Cell Rep 2012 2 42 51 22840395 PMC3408618
  60. Zhu C Zhao J Bibikova M Leverson JD Bossy-Wetzel E Fan JB Abraham RT Jiang W Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference. Mol Biol Cell 2005 16 3187 3199 15843429 PMC1165403

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Authors
Guardia, C. M., Farías, G. G., Jia, R., Pu, J., & Bonifacino, J. S.
Affiliations
National Institutes of Health (US)
Corresponding author
Bonifacino, Juan S.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2016-11
Volume
17
Issue
8
Pages
1950-1961
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2556134275
Cited by
269
References
4
Citations by year
2026: 24 · 2025: 23 · 2024: 46 · 2023: 31 · 2022: 32 · 2021: 28 · 2020: 28 · 2019: 21 · 2018: 16 · 2017: 19 · 2016: 1
FWCI
10.86
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NICHD
  • NIH (ZIA HD001607)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
lysosome transport, kinesin-1, kinesin-3, KIF5B, KIF1A, tubulin acetylation, tubulin tyrosination, dynein, lysosome positioning, bidirectional transport, small GTPases
MeSH terms
Biological Transport, Cell Membrane, Dyneins, HeLa Cells, Humans, Lysosomes, Microtubules, Models, Biological, Mutation, Kinesins, Multiprotein Complexes

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